血管外肺水、肿瘤坏死因子-α、E-选择素、血管抑制因子-2与急性呼吸窘迫综合征患者预后的相关性研究

目的：分析血管外肺水（ EVLW）、肿瘤坏死因子-α（ TNF-α）、E-选择素、血管抑制因子-2与急性呼吸窘迫综合征（ ARDS）的相关性,探讨EVLW、TNF-α、E-选择素、血管抑制因子-2在ARDS病情严重程度及预后判断中的参考价值。方法选择36例ARDS患者进行PiCCO监测,根据PiCCO监测指标血管外肺水指数（ EVLWI）的高低分为两组,EVLWI≥14 mL/kg组和EVLWI＜14 mL/kg组,监测记录患者EVLWI、PVPI、CI、ITBVI等血流动力学指标,观察患者血气分析结果,记录氧合指数、计算APACHEⅡ评分,应用ELISA方法检测两组患者血清TNF-α、E-选择素、血管抑制因子-2水平。结果 EVLWI≥14 mL/kg组患者APACHEⅡ评分为（23．93±4．44）分、28 d病死率为61．1％、ICU住院时间为（19．05±4．0） d,均较 EVLWI ＜14 mL/kg组[APACHEⅡ评分为（18．58±3．66）分、28 d病死率为27．8％、ICU住院时间为（14．35±3．39）d]高（t＝3．941,χ2＝4．050,t＝3．797,均P＜0．01）;同时血清TNF-α为（85．28±18．25）μg/L、E-选择素为（74．07±14．57）μg/L,也较EVLWI＜14 mL/kg组[TNF-α为（63．27±20．28）μg/L、E-选择素为（40．99±16．35）μg/L]高（t＝3．422、5．847,均P＜0．01）;EVLWI≥14 mL/kg组氧合指数为（122．86±25．45）,较EVLWI＜14 mL/kg组的（156．77±37．58）低（t＝-3．170,P＜0．01）。两组中28 d内仍存活的20例患者（存活组）,在入组后经72 h积极治疗后EVLWI明显下降（Z＝-0．392,P＜0．01）,氧合指数较前升高（Z＝-3．845,P＜0．01）,且TNF-α、E-选择素水平均较前下降（t＝7．194、4．025,均P＜0．01）;而死亡组16例患者经72 h积极治疗后EVLWI、TNF-α、E-选择素水平较前无下降,氧合指数较前无改善,差异无统计学意义（均P＞0．05）。 EVLWI 与PVPI、EVLWI 与TNF-α、EVLWI与E-选择素均呈显著正相关（r＝0．605、0．649、0．549,均P＜0．01）?     

妇科恶性肿瘤及异常妊娠对上呼吸道感染的影响

目的：分析妇科恶性肿瘤及异常妊娠对住院患者上呼吸道感染的影响。方法回顾性分析2012年1月-2012年12月医院妇科6507例患者的资料。根据疾病性质分为恶性肿瘤组163例及非恶性肿瘤组6344例,其中非恶性肿瘤组又分为异常妊娠组2011例及非异常妊娠组4333例,统计分析恶性肿瘤以及妊娠因素对上呼吸道感染的影响。结果共发现上呼吸道感染患者22例,其中恶性肿瘤组3例,阳性率1．84％;非恶性肿瘤组19例,阳性率0．30％。恶性肿瘤组阳性率明显高于非恶性肿瘤组（χ2＝14．11,P＜0．01）;异常妊娠组11例患上呼吸道感染,阳性率0．55％,非异常妊娠组8例患上呼吸道感染,阳性率0．18％,异常妊娠组明显高于非异常妊娠组,2组比较,差异有统计学意义（χ2＝6．04,P＜0．05）。结论恶性肿瘤以及异常妊娠患者处于免疫抑制状态,较其它病种更易导致上呼吸道感染。     

肿瘤坏死因子相关凋亡诱导配体在再生障碍性贫血患者中的表达及意义

目的通过检测再生障碍性贫血(AA)患者骨髓单个核细胞表面肿瘤坏死因子相关凋亡诱导配体(TRAIL)的表达,探讨TRAIL在AA造血干细胞凋亡中的作用。方法采用流式细胞术对12例AA患者(AA组)、11例AA治疗后缓解患者(缓解组)、12例正常对照者(对照组)骨髓单个核细胞表面TRAIL的表达进行检测。结果 AA组、缓解组、对照组TRAIL均有表达;AA组TRAIL的阳性表达率(5.8±3.3)%高于缓解组(2.4±2.0)%和对照组(3.2±2.2)%(P<0.05);缓解组与对照组间差异无统计学意义(P>0.05)。结论 TRAIL在AA患者骨髓单个核细胞表面的表达阳性率增高,提示TRAIL介导的细胞凋亡可能在AA的发病机制中发挥一定的作用。     

A novel rapid and selective enzymatic debridement agent for burn wound management: A multi-center RCT

Objectives

Excisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC.

Methods

We conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4 h) or SOC, which included surgical excisional or non-surgical debridement.

Results

NXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P < 0.0001), need for surgery (24.5% vs. 70.0%, P < 0.0001), the area of burns excised (13.1% vs. 56.7%, P < 0.0001) and the need for autografting (17.9% vs. 34.1%, P = 0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events.

Conclusions

Enzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns.

Trial registration

: Clinical Trials.gov NCT00324311.     

Predicción de resultados de cistoscopias en la práctica

ObjectiveOur objective was to elaborate a predictive model of bladder cancer, in an unselected clinical population submitted to cystoscopy.Materials and methodsWe recruited consecutive patients that underwent cystoscopy due to suspicion of bladder cancer or surveillance of a previously diagnosed bladder cancer. Urine cytology and a BTA-stat® (BTA) test were carried out for all patients. To avoid an assessment bias, the BTA-tests, cytologies and cystoscopies were conducted in a blinded fashion. We used logistic regression to predict cystoscopy results from cytology, BTA-test and clinical variables.ResultsFrom August 2011 to July 2012, we recruited 244 patients and 237 were valid for analysis. Newly diagnosed and surveillance cases were 13% and 87% respectively. Cytology and BTA-test sensitivities were 57.9% (CI 95: 42.2-72.1) and 63.2% (CI 95: 47.3-76.6) with specificities of 84.4% (CI 95: 78.7-88.8) and 82.9% (CI 95: 77.1-87.5). The predictive model included the BTA-test, cytology, time since previous tumour, and treatment with mitomicin or BGC during the last three months. The model predictive accuracy (AUC) was .85 (.78-.92), and dropped to 0.79 when excluding the BTA-test (P = .026). For the surveillance of bladder cancer, a 10% threshold on the model predicted probabilities resulted in an overall negative predictive value of 95.7%, and 95.0% in low grade tumours.ConclusionIn a cost containment environment, our prediction model could be used to space out cystoscopies in patients with previous, low grade tumours, resulting in a more efficient use of resources in the healthcare system.     

Tumor Growth Rate Provides Useful Information to Evaluate Sorafenib and Everolimus Treatment in Metastatic Renal Cell Carcinoma Patients: An Integrated Analysis of the TARGET and RECORD Phase 3 Trial Data

BackgroundResponse Evaluation Criteria in Solid Tumors (RECIST) criteria may not be sufficient to evaluate the response of targeted therapies in metastatic renal cell carcinoma (mRCC). The tumor growth rate (TGR) incorporates the time between evaluations and may be adequate.ObjectiveTo determine how TGR is modified along the treatment sequence and is associated with outcome in mRCC patients.Design, setting, and participantsMedical records from all patients prospectively treated at Gustave Roussy (IGR) in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) (sorafenib vs placebo, n = 84) and the RECORD (everolimus vs placebo, n = 43) phase 3 trials were analyzed. TGR was computed across clinically relevant periods: BEFORE treatment introduction (wash-out), UNDER (first cycle), at PROGRESSION (last cycle) and AFTER treatment discontinuation (washout). The association between TGR and outcome (overall survival [OS] and progression-free survival [PFS]) was computed in the entire TARGET cohort (n = 903).InterventionSorafenib, everolimus, or placebo.Outcome measurements and statistical analysisTGR, RECIST, OS, and PFS rates.Results and limitationsAlthough nearly all the patients (IGR) were classified as stable disease (RECIST) after the first cycle, the great majority of the patients exhibited a decrease in TGR UNDER compared with BEFORE (sorafenib: p < 0.00001; everolimus: p < 0.00001). In sorafenib-treated but not in everolimus-treated patients (IGR), TGR at PROGRESSION (last cycle) was still lower than TGR BEFORE (washout) (p = 0.012), while TGR AFTER progression (washout) was higher than TGR at PROGRESSION (last cycle) (p = 0.0012). Higher TGR (first cycle) was associated with worse PFS (hazard ratio [HR]: 3.61; 95% confidence interval [CI], 2.45–5.34) and worse OS (HR: 4.69; 95% CI, 1.54–14.39), independently from the Motzer score and from the treatment arm in the entire TARGET cohort.ConclusionsComputing TGR in mRCC patients is simple and provides clinically useful information for mRCC patients: (1) TGR is independently associated with prognosis (PFS, OS), (2) TGR allows for a subtle and quantitative characterization of drug activity at the first evaluation, and (3) TGR reveals clear drug-specific profiles at progression.     

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection

ObjectiveTo identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection.Materials and methodsWe retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods.ResultsThe median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively.ConclusionsFollowing RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.